The need to discover new classes of antibiotic compounds and/or antibiotics with different target sites is being reiterated frequently with the threat of drug resistant pathogens, reemerging pathogens and/or bio-terrorism concerns. With each passing decade, strains of virtually all important bacterial pathogens of humans have arisen that are resistant to at least one class of antibiotics, and strains resistant to multiple classes of antibiotics have become increasingly widespread. In fact, according to the Centers for Disease Control and Prevention (CDC 2000-2001), virtually all significant bacterial infections in the world are becoming resistant to the antibiotic treatment of choice. This rise is generally attributed to pathogens which have become resistant to commonly used antibiotics which focus on a limited number of target sites. Some pathogens that were generally considered historical disease causing agents are reemerging either due to genetic modifications making the organism more virulent and/or exposure to a larger portion of the world population. Related to the naturally occurring genetic modifications are intentional genetic modifications conducted by groups with bio-terrorist desires. Frequently, these intentional genetic modifications will focus on making an otherwise susceptible disease pathogen resistant to the current antibiotics with known target sites.
For Staphylococcus aureus in particular, evolving resistance mechanisms have created significant treatment challenges over the years. Beginning with penicillinase-producing strains that were resistant to conventional penicillins, the need for newer, effective antibiotics against this organism has ensued. Most recently, with the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA), traditional first-line antibiotics are once again ineffective, and, unfortunately, the prevalence of CA-MRSA is already high, accounting for well over 60% of all cases of community-associated S. aureus infections. Even worse is the recent discovery of multi-drug resistant strains of CA-MRSA that are capable of rapidly acquiring resistance to most all available agents via a plasmid-mediated mechanism. In the face of this threat, a number of new antibiotics targeted against S. aureus are under development. However, of the new antibiotics known to be in clinical development, none has a novel mechanism of action. For these reasons the need for totally new treatments for S. aureus infections is evident.
It would be advantageous to have a method for identifying compounds useful for treating S. aureus infections via a new mechanism. The present provides such a method, as well as treatment methods using the discovered compounds.